[CIS-PAGID] 10yo with lymphopenia and chronic lung disease

[Cowan, Mort]

Definitely want to consider a radiation sensitive type of leaky SCID. When she's under for lung biopsy should consider getting skin for fibroblasts. How low was the PHA response?

Mort

Morton J. Cowan, M.D.
Professor of Pediatrics
Chief, Allergy Immunology and Blood and Marrow Transplant Division
UCSF Children's Hospital, Room M659
505 Parnassus Ave
San Francisco, CA 94143-1278
 
Phone: 415-476-2188
FAX: 415-502-4867
 
**Confidentiality Notice** This email communication and any attachments may contain confidential and privileged information for the use of the designated recipients named above. Distribution, reproduction or any other use of this transmission by any party other than the intended recipient is prohibited.


-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Routes, John
Sent: Tuesday, April 03, 2012 4:05 PM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS-PAGID] 10yo with lymphopenia and chronic lung disease

Panida
I have a few questions---Has the patient always been lymphopenic? Do you have prior CBCs or lymphocyte subset analysis? Is the patient on immunosuppressives, in particular steroids (which can cause a profound lymphopenia of both B and T cells even on relatively small doses). In regard to the lung disease-Do you have complete pulmonary function tests including plethysmography (lung volumes, Dlco, pre-post bronchodilator response)? Is the diagnosis of "asthma" tentative or do you have evidence of reversible obstructive disease? Can you describe more fully the extent of lung involvement by CT of the chest. For example, we have seen cases of marked T cell lymphopenia associated with marked lung parenchymal lung disease characterized by lymphocytic infiltration-this can occur fairly commonly with (CVID) or without immunodeficiency (sarcoidosis).

Another question is whether the lung disease has contributed to the FTT or if it is secondary to an immunodeficiency. The fact that she can make specific Ab to pneumococcus and  diptheria I think would argue against a leaky SCID, although I defer to Kate and Gigi as they have much more expertise in this area than I do. Assuming the patient can tolerate it, I believe an open lung biopsy is essential in this case. I would also suggest TCR spectratyping to look for oligoclonality---the best way now is by deep DNA sequencing, but conventional spectratyping would be fine to answer the question of leaky SCID.

Sincerely
Jack Routes



John M. Routes, MD
Chief, Section of Allergy and Clinical Immunology Co-Director, Clinical and Translational Science Institute of Southeast WI Professor of Pediatrics, Medicine, Microbiology and Molecular Genetics Department of Pediatrics Children's Hospital of Wisconsin Medical College of Wisconsin
9000 W. Wisconsin Ave.
Milwaukee, WI  53226-4874

Phone: 414-456-4802; 414-266-6997
Fax: 414-456-6487 (Clinical)
Fax: 414-456-6323 (Laboratory)
Email: jroutes at mcw.edu




________________________________
From: "Sriaroon, Panida" <psriaroo at health.usf.edu>
Reply-To: "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>
Date: Tue, 3 Apr 2012 11:48:01 -0500
To: "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>
Subject: [CIS-PAGID] 10yo with lymphopenia and chronic lung disease

Dear all,

I have an interesting 10yo Caucasian female who has had chronic lung disease with severe lymphopenia. Other history includes recurrent ear and sinus infection and failure to thrive (wt 1%ile, height 10%ile). She has been diagnosed with severe persistent asthma for the past several years. Lately, was noted to have clubbing of digits and hypoxia (SpO2 85% room air). She has never had bronchoscopy to date. Her immunologic profile is as following:

IgG 1020, IgA 573, IgM 157 mg/dL. Tetanus titer 0.59, Diphtheria titer 0.07, pneumo titers protective in 4 serotypes.
[cid:3416321105_5560998]
Absolute lymphocyte count of 363 with WBC of 4500, leukocyte of 7%, neutrophils being 81%. Absolute CD3 was 70. Absolute CD4 of 35. Absolute CD8 of 18. Absolute CD19 of 62. Absolute natural killer cell of 224. The T4-to-T8 ratio was 2. Mitogen study shows low response to PHA, ConA and Pokeweed. These were drawn when off oral steroids. In 2007, her ALC was around 600.

Per report, a chest CT showed bilateral peribronchial nodular opacities with hazy ground glass opacities in the bilateral upper lobes. No comments on thymus.
Sinus CT showed mucosal thickening and maxillary sinus bilaterally.

Recent work up is negative for HIV infection, CF, ciliary dyskinesia, FISH for DiGeorge, DHR, and TB-quantiferon gold. Nasopharyngeal viral culture is negative for common virus. ADA and PNP levels are normal. She is currently on Septra and azithromycin prophylaxis as well as asthma inhaler meds.

Any comments on the Dx and work ups? Since she is making antibodies we are thinking Nezelof's syndrome and leaky SCIDs. Genetic testings for AR SCID (Jak-3, IL-7R, RAG-1/2, Artemis, CD3delta, CD3epsilon) were sent to Correlagen and those are still pending. Now we are planning to admit her for a lung/lymph node biopsy and evaluation for possible BMT. Is it possible that her T/plasma cells are accumulating in lungs or other organs? Has anyone seen a case similar to this pt?

Any thoughts are appreciated.
Panida

Panida Sriaroon, MD
Assistant Professor
Division of Allergy, Immunology, and Rheumatology USF/All Children's Hospital Beeper 727.825.4379 Office 727.553.3521 E-mail:psriaroo at health.usf.edu